Pseudomonas aeruginosa is an important human pathogen, particularly in the setting of altered immunity. The high morbidity and mortality of these infections has been linked to exotoxin A, potent inhibitor of protein synthesis. Patients with Pseudomonas aeruginosa bacteremia were shown to be more likely to survive if they have high titers of antibodies against exotoxin A prior to the onset of infection. The exact pathogenic role of this toxin in pseudomonas sepsis, however, remains unknown. In this investigation, we plan to clarify the relationship between in vivo exotoxin A release and the pathophysiology of pseudomonas septicemia. Serum exotoxin A levels will be determined in both canines and humans with pseudomonas bacteremia using an ELISA assay and the circulating concentrations of exotoxin A will be compared to cardiovascular changes and outcome. Human isolates of Pseudomonas aeruginosa will be examined in vitro for the ability to produce exotoxin A (Western blot method) and this will be correlated with the course and outcome of the infection produced by individual strains. This investigation will provide insight into the role of bacterial toxins in the pathogenesis of septicemia and provide a basis for new antitoxin therapies.